TY - JOUR
T1 - LEBER CONGENITAL AMAUROSIS DUE TO CEP290 MUTATIONS-SEVERE VISION IMPAIRMENT WITH A HIGH UNMET MEDICAL NEED
T2 - A Review
AU - Leroy, Bart P.
AU - Birch, David G.
AU - Duncan, Jacque L.
AU - Lam, Byron L.
AU - Koenekoop, Robert K.
AU - Porto, Fernanda B.O.
AU - Russell, Stephen R.
AU - Girach, Aniz
N1 - Publisher Copyright:
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.
PY - 2021/5/1
Y1 - 2021/5/1
N2 - PURPOSE: Leber congenital amaurosis due to CEP290 mutations (LCA10) is an inherited retinal disease that often results in severe visual impairment or blindness in early childhood. Currently, there are no approved treatments, highlighting the considerable unmet medical need associated with LCA10. We aimed to review the clinical characteristics of LCA10, its impact on patients and society, and the investigational treatment strategies currently in development. METHODS: Review of the current literature. RESULTS: LCA10 is an autosomal recessive ciliopathy, for which the CEP290 intronic variant c.2991+1655A>G (p.Cys998X) is the most common mutation. Usually diagnosed in early childhood, most patients with LCA10 have severe visual impairment during their first decade of life, which significantly affects the quality of life and development. LCA10 also has a significant societal burden (direct and indirect costs). RNA editing using antisense oligonucleotides or Staphylococcus aureus CRISPR-associated protein-9 nuclease is currently under investigation for treatment of p.Cys998X LCA10. Specifically, the antisense oligonucleotide therapy QR-110 (sepofarsen) has demonstrated encouraging safety and efficacy data in a first-in-human trial; a phase 3 clinical trial is ongoing. CONCLUSION: Interventions that can preserve or improve vision in patients with LCA10 have considerable potential to improve the patient quality of life and reduce burden of disease.
AB - PURPOSE: Leber congenital amaurosis due to CEP290 mutations (LCA10) is an inherited retinal disease that often results in severe visual impairment or blindness in early childhood. Currently, there are no approved treatments, highlighting the considerable unmet medical need associated with LCA10. We aimed to review the clinical characteristics of LCA10, its impact on patients and society, and the investigational treatment strategies currently in development. METHODS: Review of the current literature. RESULTS: LCA10 is an autosomal recessive ciliopathy, for which the CEP290 intronic variant c.2991+1655A>G (p.Cys998X) is the most common mutation. Usually diagnosed in early childhood, most patients with LCA10 have severe visual impairment during their first decade of life, which significantly affects the quality of life and development. LCA10 also has a significant societal burden (direct and indirect costs). RNA editing using antisense oligonucleotides or Staphylococcus aureus CRISPR-associated protein-9 nuclease is currently under investigation for treatment of p.Cys998X LCA10. Specifically, the antisense oligonucleotide therapy QR-110 (sepofarsen) has demonstrated encouraging safety and efficacy data in a first-in-human trial; a phase 3 clinical trial is ongoing. CONCLUSION: Interventions that can preserve or improve vision in patients with LCA10 have considerable potential to improve the patient quality of life and reduce burden of disease.
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U2 - 10.1097/IAE.0000000000003133
DO - 10.1097/IAE.0000000000003133
M3 - Article
C2 - 33595255
AN - SCOPUS:85105760323
VL - 41
SP - 898
EP - 907
JO - Retina
JF - Retina
SN - 0275-004X
IS - 5
ER -